An alternative approach to understand schizophrenia: polyamines hypothesis through NMDA receptors

Abstract

The glutamate hypothesis of schizophrenia based on the observations that administration of drugs that block N-methyl-D-aspartate (NMDA) glutamate receptors could induce schizophrenia-like symptoms. There are several evidences linking abnormal glutamatergic transmission to cognitive, negative, and positive symptoms of schizophrenia and the glutamatergic system is now a major focus for the development of new compounds in schizophrenia.The polyamines are omnipresent aliphatic molecules comprising putrescine, spermidine, spermine and agmatine. The polyamines and their biosynthetic enzymes are found throughout the body, including the central nervous system (CNS), where they display specific regional distributions in the CNS. The polyamines have an important role in the modulation of cell growth and on cell membrane functions. It was hypothesized that schizophrenia may be related to a general abnormality in neuronal membranes. Agmatine, a polyamine, selectively blocks the NMDA subclass of glutamate receptors in rat hippocampal neurons. There are several evidence indicate that a relationship between polyamines and etiopatogenezis of schizophrenia. Here, in this rewiev, a new approach for understanding schizophrenia via NMDA receptors and their interaction with agmatine which is a biological active polyamine transmitter in brain is proposed.